AGE-DEPENDENCE AND MODULATION BY GONADECTOMY OF THE SEX-SPECIFIC RESPONSE OF RAT DIAPHYSEAL BONE TO GONADAL-STEROIDS

We have previously reported that diaphyseal bone of prepubertal rats responds in a sex-specific manner to gonadal steroids, 24 h after steroid injection, by increases in creatine kinase (CK) specific activity and the rate of DNA synthesis. We have also shown that hormonal intervention abolished the sex-specific response of diaphyseal bone to sex steroids. In the present study, we examined the responsiveness of diaphyseal bone and cartilage to gonadal steroids in male and female Wister-derived rats at ages between 5 days and 1 yr. In both diaphyseal bone and cartilage of untreated control rats, a peripubertal peak of CK specific activity was seen, which was more pronounced in females. Diaphyseal bone, unlike epiphyseal cartilage, responded specifically to a single injection of 17 beta-estradiol (E(2); 5 mu g/rat) in females and to 5 alpha-dihydrotestosterone (DHT; 50 mu g/rat) in males. The highest response occurred peripubertally, but was skewed toward prepubertal ages in males and postpubertal ages in females. To study the effect of gonadectomy on this sex-specific response of diaphyseal bone, rats were gonadectomized at the age of 24 or 180 days and from 4 days to 4 weeks thereafter were challenged with either E(2) or DHT. Diaphyseal bones of gonadectomized rats of either sex responded to both Ep and DHT, beginning 7 days after surgery. Thus, in gonadectomized rats, there was a loss of the sex specificity of response to steroid hormones, which could be restored by replenishment, by five daily injections, of the characteristic hormone of each sex. In the epiphyseal cartilage, the same replenishment schedule resulted in acquisition of a sex-specific response in both sexes, not seen previously. These data in conjunction with the previously reported hormonal modulation of sex-specific responses, are consistent with a developmental acquisition of diaphyseal sex steroid specificity that requires for its maintenance the presence of appropriate amounts of the characteristic gonadal steroid in each sex.